crossing96/oncoscreening huggingface dataset:
CCDC137 knockdown suppresses bladder cancer progression by downregulating SCD.	BACKGROUND: The Coiled-coil domain-containing (CCDC) family, due to its unique protein structural domain and broad involvement in diverse biological processes, has emerged as a focus in oncology research. Nevertheless, its clinical significance and function in bladder cancer (BLCA) remain poorly defined. METHODS: Machine learning algorithms were employed to identify pivotal CCDC genes in the cancer genome atlas (TCGA), and a prognostic model was subsequently constructed. Multi-omics data encompassing pan-cancer cohorts, single-cell sequencing, and spatial transcriptomics were integrated to characterize the expression patterns and prognostic significance of Coiled-coil domain-containing 137 (CCDC137), a previously uncharacterized CCDC family member in BLCA. Tissue microarray confirmed CCDC137 abnormal expression in bladder carcinoma specimens. The effect of CCDC137 knockdown on BLCA progression was evaluated through CCK8 assay, clonogenic formation, wound healing, Transwell, and subcutaneous xenograft models. RNA sequencing, quantitative RT-PCR, and western blot were utilized to delineate its regulatory network. RESULTS: A prognostic model incorporating 10 CCDC genes was successfully established in the TCGA-BLCA cohort. Then, we found that CCDC137 exhibited pan-cancer overexpression and usually correlation with poor clinical outcomes. Immunohistochemistry further substantiated its dysregulation in bladder carcinoma. Integrated multi-omics analyses suggested associations between CCDC137 expression and a tumor immunosuppressive microenvironment. CCDC137 knockdown significantly suppressed bladder cancer cell proliferation and migratory capacity in vitro. Correspondingly, subcutaneous xenograft tumor growth was inhibited in vivo. Moreover, decreased expression of stearoyl-CoA desaturase (SCD), a key lipid metabolic enzyme, accompanied CCDC137 depletion. These findings collectively suggest a cancer-promoting role for CCDC137 in bladder carcinoma. CONCLUSIONS: This systematic investigation combining multi-omics bioinformatics analyses and experimental validation demonstrates the role of CCDC137 in bladder carcinoma progression, providing novel mechanistic insights into the pathogenesis of BLCA and offering a theoretical foundation for therapeutic targeting of CCDC137 in urothelial malignancies.	bladder
Mitomycin Intravesical Solution: First Approval.	Mitomycin intravesical solution (ZUSDURI(TM)), a hydrogel formulation of the DNA synthesis inhibitor mitomycin, has been developed by UroGen Pharma, Inc. for the treatment of low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC) via intravesical instillation. In June 2025, mitomycin intravesical solution was approved for the treatment of recurrent LG-IR-NMIBC in the USA. This article summarizes the milestones in the development of mitomycin intravesical solution leading to this first approval for LG-IR-NMIBC.	bladder
ROS-responsive resiquimod prodrug nanoparticles for macrophage reprogramming and enhanced immune checkpoint inhibitor therapy in bladder cancer.	Bladder cancer remains a formidable challenge, especially for patients who fail to respond adequately to immune checkpoint inhibitors (ICIs). The suboptimal efficacy of current treatments underscores an urgent need for more effective immunomodulatory strategies. Here, we propose a ROS-responsive resiquimod (R848) prodrug (R-P) that improves drug delivery and reshapes the immunosuppressive tumor microenvironment. Clinical data from The Cancer Genome Atlas and patient samples underscore the therapeutic value of targeting CD206 and TLR7/8 to repolarize tumor-associated macrophages. The prodrug R-P is created by conjugating a phenylboronic acid pinacol ester moiety to R848 via a succinic anhydride linker, enabling the prodrug to remain stable in systemic circulation while releasing its parent compound in the oxidative tumor microenvironment, thereby minimizing off-target effects. Further, mannose-functionalized nanoparticles (R-P@APM-DPs) achieve an impressive loading capacity of R848 (34.3 %) and exhibit robust ROS-responsive release. In a murine MB49 bladder cancer model, R-P@APM-DPs significantly reduce tumor growth, enhance M1 macrophages, and increase CD8(+) and CD4(+) T cells, while decreasing the number of immunosuppressive cells. Notably, combination therapy with anti-PD-1 leads to a potent anticancer response in both MB49-bearing mice and patient-derived organoids. This synergy highlights the translational potential of a ROS-responsive prodrug approach for enhancing ICI-based immunotherapies.	bladder
Adjuvant nivolumab in muscle-invasive urothelial carcinoma: exploratory biomarker analysis of the randomized phase 3 CheckMate 274 trial.	Nivolumab monotherapy has been approved for the adjuvant treatment of adult patients with urothelial carcinoma who are at high risk of recurrence after undergoing radical resection of urothelial carcinoma based on results of the phase 3 CheckMate 274 trial, in which adjuvant nivolumab versus placebo demonstrated improvement in the primary endpoint of disease-free survival (DFS) in high-risk muscle-invasive urothelial carcinoma (MIUC). Identification of biomarkers associated with treatment outcomes can help refine patient selection, and inform on the immunobiology of disease. To assess the relevance of key biomarkers in the adjuvant MIUC setting, extensive exploratory analyses of tumor biomarkers, including associations with DFS, were performed. Differential gene expression and gene signature analysis found that immune-related genes and pathways, in particular a high interferon-γ signature, were predictive of improved DFS in nivolumab-treated patients. Positive predictive and prognostic associations, respectively, were found for CD4 gene expression and measures of CD8 T cell infiltration. A composite predictive model suggested that high tumor cell PD-L1 expression, high CD4 gene expression, high tumor mutational burden score, receipt of neoadjuvant cisplatin and low transforming growth factor-β gene signature score made the greatest contributions to predicting improved outcomes in nivolumab-treated patients. These results reinforce studies establishing the importance of tumor biomarkers of adaptive immunity in influencing response to PD-1-PD-L1 blockade, indicating the potential predictive rather than solely prognostic nature of such findings. ClinicalTrials.gov identifier: NCT02632409 .	bladder
Comparison of molecular profiles (Nectin-4 and TROP-2) in upper tract urothelial carcinoma with a positive history of urinary bladder cancer vs. UTUC only in the era of ADCs.	Upper tract urothelial carcinoma (UTUC) and urinary bladder cancer (UBC), though histologically similar, differ molecularly, prompting interest in their biomarker profiles for targeted therapies like antibody-drug conjugates (ADCs) enfortumab vedotin (targeting Nectin-4) and sacituzumab govitecan (targeting TROP-2). This study investigated Nectin-4 and TROP-2 expression in 87 UTUC patients, including 54 with a history of concurrent UBC (UTUC + UBC) and 33 with UTUC alone. Immunohistochemical analysis revealed widespread TROP-2 expression (98.8% of samples), with high levels linked to low-grade UTUC (p = 0.043) and intense staining (mean H-score 227 ± 63) across both cohorts. Nectin-4 was expressed in 70.1% of samples overall but was more frequent in the UTUC + UBC group (88.8% vs. 63.6% in UTUC-only patients), though this difference lacked statistical significance (p = 0.340). Notably, Nectin-4 staining intensity was weak in both groups (mean H-score 66 ± 65), suggesting biological distinctions between UTUC with and without UBC. The findings imply that ADCs targeting TROP-2 and Nectin-4 may hold therapeutic promise in UTUC without requiring prior biomarker testing. Additionally, the elevated Nectin-4 expression in UTUC + UBC patients hints at divergent molecular pathways that could influence treatment strategies, warranting further clinical exploration.	bladder
Advances in the immunological microenvironment and immunotherapy of bladder cancer.	Bladder cancer remains a significant global health challenge, particularly affecting male populations. While radical cystectomy and chemotherapy have been mainstays of treatment, their substantial morbidity and impact on quality of life have driven the development of bladder-preserving immunotherapeutic strategies. Clinical trial data support the use of ICIs as first-line therapy for cisplatin-ineligible patients, second-line treatment for platinum-refractory disease, and maintenance therapy. This review comprehensively summarizes the advances in bladder cancer immunotherapy, focusing on the tumor immune microenvironment and emerging treatment modalities, as well as the roles of immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4 pathways, which have demonstrated remarkable efficacy in both muscle-invasive (MIBC) and non-muscle invasive bladder cancer (NMIBC). This review also provides novel approaches including combination immunotherapies, tumor vaccines, adoptive cellular therapies, and oncolytic viruses. Overall, these immunotherapeutic advances are transforming bladder cancer management, offering improved outcomes while reducing treatment morbidity.	bladder
SEOM-SOGUG clinical guideline for urothelial cancer (2025).	This clinical guideline provides evidence-based recommendations for the diagnosis, staging, and management of bladder cancer across all disease stages. In these guidelines (updated in 2025), we summarize current evidence and available therapies for the medical management of urothelial cancer.	bladder
Management of clinical stage T3/T4 bladder cancer: a review.	INTRODUCTION: Bladder cancer is a common malignancy in the United States and while the majority are non-muscle invasive at diagnosis, those with muscle-invasive and locally advanced disease can be challenging to manage. In addition, the prognosis is poorer in this group with high rates of recurrence following treatment. Clinical trials and advances in systemic therapy have helped to improve outcomes for these patients. MATERIALS/METHODS: Articles were chosen for inclusion based on expert knowledge of the literature and PubMed literature searches for the relevant areas, with a focus on clinical trials. Appropriate articles were selected for inclusion by reviewing article titles, abstracts and full texts. RESULTS: The standard of care for treatment of muscle invasive bladder cancer involves neoadjuvant chemotherapy followed by radical cystectomy. The NIAGARA trial recently changed the standard of care to include immunotherapy both in the neoadjuvant and adjuvant settings. Multiple clinical trials have assessed the potential benefit of adjuvant immunotherapy in patients with high-risk disease after radical cystectomy, leading to the approval of nivolumab in this setting. Improvements in staging and surveillance of these patients are necessary. The use of circulating tumor DNA and advances in imaging have also shown promise in prognostication and detection and monitoring of recurrence. CONCLUSIONS: Locally advanced bladder cancer is a challenging condition to manage, and while advances have been made in systemic therapy and biomarkers such as circulating tumor DNA, further investigation is needed to continue to improve outcomes for this group of patients.	bladder
Virus-induced APOBEC3 transmutagenesis in bladder cancer initiation.	"Carcinogenesis in human urothelium is driven by a high burden of mutations caused by the antiviral ""APOBEC3"" (apolipoprotein B mRNA editing enzyme, catalytic subunit-like 3) cytosine deaminase enzymes; however, there is no established viral etiology. BK polyomavirus (BKPyV) is a ubiquitous childhood infection that persists in the kidney during adulthood and is frequently detected in urine. Chronic BKPyV infections of normal human urothelium induced an innate response, including apical extrusion of infected cells. Local paracrine interferon signaling induced APOBEC3 expression in both infected and juxtaposed bystander cells, leading to acquisition of hallmark APOBEC3-mediated mutational signatures that recapitulated the variation in mutational character found in patients with muscle-invasive bladder cancer. In our model for urothelial carcinogenesis, uninfected bystander cells witnessing BKPyV infection become APOBEC3 damaged, escape extrusion, and acquire hypermutable advantage. ""Transmutagenesis"" explains how cells proximal to infected neighbors acquire cancer-initiating mutations. This hypothesis for how urothelial cancers can develop as APOBEC3 signature rich, while remaining virus-negative, suggests that a large proportion of urothelial carcinomas may be preventable by antiviral intervention."	bladder
Urinary microbiome in non-muscle invasive bladder cancer: impact of sample types and sex differences.	BACKGROUND: Previous research on urinary microbiomes in bladder cancer patients has yielded inconsistent results, highlighting the need for further investigation. This study aims to analyze microbiome dysbiosis in bladder cancer patients by comparing multiple sample types, incorporating negative controls, and assessing sex-based variations. Fifty patients who required transurethral resection of bladder tumor for treatment were selected. Three types of specimens were collected from each patient: midstream urine, catheterized urine, and normal bladder mucosal tissue. Microbiome was analyzed via 16 S rRNA gene amplificon sequencing. RESULTS: Beta diversity analysis revealed significant differences in microbiome composition between mucosal tissue and urine samples, while no significant variation was observed between midstream and catheterized urine samples. Due to the low biomass of mucosal tissue-characterized by dominance of a few taxa and high variability across extraction kit lots-its susceptibility to contamination compromised reproducibility, leading to a focus on urine samples for further analysis. Midstream urine samples showed significant sex-related microbiome differences, whereas catheterized urine exhibited no such differences, suggesting midstream urine may not be ideal for bladder-specific microbiome studies. Catheterized urine analysis identified Curvibacter, particularly Curvibacter gracilis, as significantly more abundant in bladder cancer patients compared to controls, while overall microbiome composition remained unchanged between the groups. Curvibacter prevalence was not directly correlated with any single clinical marker but increased with bladder cancer severity when patients were classified into high-risk and low-risk groups based on biopsy and clinical criteria. CONCLUSIONS: This study highlights the importance of selecting appropriate sample types for bladder microbiome analysis, with catheterized urine emerging as the most reliable option. The findings suggest that Curvibacter may be associated with bladder cancer severity, warranting further investigation into its potential role as a biomarker. Future research should focus on validating these findings in larger cohorts and exploring the mechanistic link between microbiome alterations and bladder cancer progression.	bladder
Adjuvant nivolumab versus placebo for high-risk muscle-invasive urothelial carcinoma: 5-year efficacy and ctDNA results from CheckMate 274.	BACKGROUND: Despite surgery, recurrence rates remain high in muscle-invasive urothelial carcinoma (MIUC). The phase III randomized, double-blind, multicenter CheckMate 274 trial comparing adjuvant nivolumab versus placebo in patients with high-risk MIUC after radical surgery demonstrated that adjuvant nivolumab improved disease-free survival (DFS) versus placebo. We report results with 5-year minimum follow-up including exploratory analyses of circulating tumor DNA (ctDNA). PATIENTS AND METHODS: Eligible patients had radical surgery (R0, with negative surgical margins) within 120 days before being randomized, with or without neoadjuvant cisplatin-based chemotherapy. Overall, 709 patients with MIUC at high risk of recurrence after surgery were randomly assigned 1:1 to nivolumab 240 mg or placebo every 2 weeks for ≤1 year. The primary endpoint was DFS. Overall survival (OS) was a key secondary endpoint. In a post hoc exploratory analysis, baseline ctDNA was measured using the Signatera assay. RESULTS: Median DFS was 21.9 months [95% confidence interval (CI) 18.8-36.9 months] with nivolumab versus 11.0 months (95% CI 8.3-16.6 months) with placebo in all randomized patients [hazard ratio (HR) 0.74, 95% CI 0.61-0.90], and 55.5 months (95% CI 25.8-66.5 months) versus 8.4 months (95% CI 5.6-20.0 months) in patients with tumor programmed death-ligand 1 expression ≥1% (HR 0.58, 95% CI 0.42-0.79). In all randomized patients, median OS was 75.0 months (95% CI 56.7 months-not estimable) with nivolumab versus 50.1 months (95% CI 38.0-72.1 months) with placebo (HR 0.83, 95% CI 0.67-1.02). Baseline ctDNA after radical surgery was detected in 54 (40.6%) of 133 assessable patients. Median DFS was 52.1 months (95% CI 19.4 months-not estimable) versus 5.0 months (95% CI 2.8-6.5 months) in patients with undetectable versus detectable ctDNA at baseline (HR 0.30, 95% CI 0.18-0.48). In patients included in the ctDNA analysis who had detectable ctDNA, the median DFS HR for nivolumab-treated patients versus placebo-treated patients was 0.35 (95% CI 0.18-0.66), while in patients with undetectable ctDNA, the HR for nivolumab-treated patients versus placebo-treated patients was 0.99 (95% CI 0.51-1.93). There were no new safety signals. CONCLUSIONS: Five-year results confirm durable DFS benefit and consistent safety profile for adjuvant nivolumab in high-risk MIUC. Post hoc exploratory ctDNA assessment identified patients at highest risk of recurrence and may inform tailored adjuvant therapy strategies, pending further validation.	bladder
Transglutaminase 2 facilitates metastasis of basal-like bladder cancer by sustaining MVP-mediated MAPK/ERK1/2 signaling activation.	Basal-like bladder cancer is a subtype of bladder cancer (BC) with a high risk of invasion and metastasis, for which there are currently no approved or clinically validated targeted therapies. Transglutaminase 2 (TG2) is dysregulated in various solid tumors, including muscle-invasive BC, but its role in the progression of basal-like BC remains unexplored. In this study, we revealed that TG2 is overexpressed in basal-like BC and correlates with basal/squamous cell differentiation, advanced clinical stage, poor prognosis, and lymphatic metastasis. Functional studies demonstrate that TG2 promotes epithelial-mesenchymal transition (EMT), cell migration, invasion, lymphangiogenesis, lymphatic and distant metastasis both in vitro and in vivo. Mechanistically, TG2 binds to major vault protein (MVP), which stabilizes MVP by inhibiting ubiquitin-proteasomal degradation. This process is dependent on the cross-linking activity of the transamidase of TG2. Accumulation of MVP protein facilitates MAPK/ERK1/2 signaling activation, thereby inducing EMT and malignant phenotypes. Pharmacological inhibition of TG2's catalytic activity with NC9 reduces MVP protein stability, ERK1/2 activation, and aggressive behaviors. Crucially, administration of NC9 retards the growth and EMT of patient-derived organoids (PDOs) from basal-like BC in a dose-dependent manner. Furthermore, in vivo studies validated that NC9 significantly reduces lung metastasis and is well-tolerated, with no observed significant organ toxicity. Our findings establish TG2 as a prognostic biomarker and therapeutic target, with its transamidase-dependent MVP-ERK1/2 axis offering a novel therapeutic strategy against basal-like BC.	bladder
Clinical applications of bladder magnetic resonance imaging: Beyond the VI-RADS® classification.	Bladder cancer is a cause for serious concern due to its high prevalence and the considerable challenges it poses in terms of morbidity, costs, and mortality. In recent years, magnetic resonance imaging (MRI) of the bladder has proved to be a useful tool with a significant impact on both local staging and the assessment of neoadjuvant treatment responses. This article reviews the main anatomical, histological and radiological characteristics of bladder neoplasms, describes bladder MRI, explains the VI-RADS® classification-which should only be used to classify malignant lesions and in studies undertaken principally to evaluate the probability of tumour infiltration in the muscular layer-and specifies how this technique can optimise the clinical management of patients with bladder neoplasms.	bladder
Multi-omics integrative analysis of the mechanisms linking environmental pollutant exposure to bladder cancer pathogenesis.	"Bladder cancer (BCa), the most prevalent malignancy of the urinary system, is strongly associated with environmental factors including smoking and industrial chemical exposure. Although previous studies have explored the relationship between various environmental pollutants and BCa mechanisms, there is still a need for an in-depth analysis of the specific effects and particular roles of these pollutants. This study investigates the molecular mechanisms linking environmental pollutant exposure to bladder carcinogenesis through a multi-omics integrative analysis that systematically elucidates the environment-gene interaction network. By integrating transcriptomic data from multiple BCa cohorts with the Comparative Toxicogenomics Database (CTD) gene-chemical-disease network, we identified 168 environment-responsive differentially expressed genes (DEGs). Subsequent Mendelian Randomization (MR), Summary-data-based MR (SMR), and colocalization analyses revealed three causal hub genes (CTSK, GSTM5, and PAFAH1B3; PP4 > 0.70) and associated them with 34 high-risk environmental pollutants. Molecular docking demonstrated strong binding affinities between these hub genes and more than ten pollutants, with bisphenol A, sodium arsenite, and tetrachlorodibenzodioxin (TCDD) differentially regulating distinct targets: significantly suppressing tumor-suppressor genes CTSK (OR = 0.91, p = 0.004) and GSTM5 (OR = 0.77, p < 0.001) while upregulating the oncogenic factor PAFAH1B3 (OR = 2.11, p < 0.001). Single-cell RNA sequencing (scRNA-seq) analysis and Human Protein Atlas (HPA) database validation confirmed tissue-specific expression patterns of these hub genes in bladder tissues. Our findings establish a comprehensive evidence chain connecting ""environmental pollutant exposure - gene interaction - bladder carcinogenesis,"" providing novel biomarkers and preventive targets for molecular subtyping and precision prevention of environmentally associated BCa."	bladder